Folate receptor alpha peptide vaccine generates immunity in breast and ovarian cancer patients

Kimberly R. Kalli, Matthew S Block, Pashtoon M. Kasi, Courtney L. Erskine, Timothy James Hobday, Allan B Dietz, Douglas Padley, Michael Gustafson, Barath Shreeder, Danell Puglisi-Knutson, Daniel W Visscher, Toni K. Mangskau, Glynn Wilson, Keith L Knutson

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose: Folate receptor alpha (FR) is overexpressed in several cancers. Endogenous immunity to the FR has been demonstrated in patients and suggests the feasibility of targeting FR with vaccine or other immune therapies. CD4 helper T cells are central to the development of coordinated immunity, and prior work shows their importance in protecting against relapse. Our previous identification of degenerate HLA-class II epitopes from human FR led to the development of a broad coverage epitope pool potentially useful in augmenting antigen-specific immune responses in most patients. Patients and Methods: We conducted a phase I clinical trial testing safety and immunogenicity of this vaccine, enrolling patients with ovarian cancer or breast cancer who completed conventional treatment and who showed no evidence of disease. Patients were initially treated with low-dose cyclophosphamide and then vaccinated 6 times, monthly. Immunity and safety were examined during the vaccine period and up to 1 year later. Results: Vaccination was well tolerated in all patients. Vaccine elicited or augmented immunity in more than 90% of patients examined. Unlike recall immunity to tetanus toxoid (TT), FR T-cell responses developed slowly over the course of vaccination with a median time to maximal immunity in 5 months. Despite slow development of immunity, responsiveness appeared to persist for at least 12 months. Conclusions: The results demonstrate that it is safe to augment immunity to the FR tumor antigen, and the developed vaccine is testable for therapeutic activity in most patients whose tumors express FR, regardless of HLA genotype.

Original languageEnglish (US)
Pages (from-to)3014-3025
Number of pages12
JournalClinical Cancer Research
Volume24
Issue number13
DOIs
StatePublished - Jul 1 2018

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Folate Receptor 1
Subunit Vaccines
Ovarian Neoplasms
Immunity
Breast Neoplasms
Vaccines
Epitopes
Vaccination
Safety
Clinical Trials, Phase I
Tetanus Toxoid
Histocompatibility Antigens Class II
Neoplasm Antigens
Helper-Inducer T-Lymphocytes
Cyclophosphamide
Neoplasms
Therapeutics
Genotype

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Folate receptor alpha peptide vaccine generates immunity in breast and ovarian cancer patients. / Kalli, Kimberly R.; Block, Matthew S; Kasi, Pashtoon M.; Erskine, Courtney L.; Hobday, Timothy James; Dietz, Allan B; Padley, Douglas; Gustafson, Michael; Shreeder, Barath; Puglisi-Knutson, Danell; Visscher, Daniel W; Mangskau, Toni K.; Wilson, Glynn; Knutson, Keith L.

In: Clinical Cancer Research, Vol. 24, No. 13, 01.07.2018, p. 3014-3025.

Research output: Contribution to journalArticle

Kalli, Kimberly R. ; Block, Matthew S ; Kasi, Pashtoon M. ; Erskine, Courtney L. ; Hobday, Timothy James ; Dietz, Allan B ; Padley, Douglas ; Gustafson, Michael ; Shreeder, Barath ; Puglisi-Knutson, Danell ; Visscher, Daniel W ; Mangskau, Toni K. ; Wilson, Glynn ; Knutson, Keith L. / Folate receptor alpha peptide vaccine generates immunity in breast and ovarian cancer patients. In: Clinical Cancer Research. 2018 ; Vol. 24, No. 13. pp. 3014-3025.
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AU - Kalli, Kimberly R.

AU - Block, Matthew S

AU - Kasi, Pashtoon M.

AU - Erskine, Courtney L.

AU - Hobday, Timothy James

AU - Dietz, Allan B

AU - Padley, Douglas

AU - Gustafson, Michael

AU - Shreeder, Barath

AU - Puglisi-Knutson, Danell

AU - Visscher, Daniel W

AU - Mangskau, Toni K.

AU - Wilson, Glynn

AU - Knutson, Keith L

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